Streptococcus pneumoniae is the most common cause of community acquired pneumonia with high morbidity and mortality worldwide. A major feature of pneumococcal pneumonia is an abundant neutrophil (PMNs) infiltration. We have found that the wild-type D39 strain and the CPS2E strain, a non encapsulated isogenic mutant of D39 lacking only the gene cps2E, stimulated superoxide anion (O2-), evaluated by cytochrome c reduction, similarly. But a non-encapsulated R6 strain, containing also a deletion starting from cps B to cps G genes, amplified the oxidative burst. The R6 strain activated neutrophil NADPH oxidase to produce reactive oxygen intermediates, as demonstrated by the traslocation of its cytosolic subunits p47phox to the plasma membrane. This activity was completely inhibited by wortamannin and bisidolylmaleimide but not by SB-203580. Taken together these finding strongly suggest that R6 strain activates pathways involving PKC and PI-3 Kinase dependent reactions. In order to know whether modulation of neutrophil functions induced by R6 strain was selective for oxygen metabolism we studied secretion of -glucoronidase, a marker of degranulation. We have found that PMNs incubated with D39 and R6 strains secreted similar levels of -glucoronidase and their effects were lower than that of the standard agonist fMLP. On the basis of these observations, we conclude that pneumococcal expression of genes cps B, C e D modulates neutrophil respiratory burst activity and thus may facilitate chronic persistent infection by Streptococcus pneumoniae.

CPS genes of Streptococcus pneumoniae modulate inflammatory response of neutrophils

MONTEMURRO, Pasqualina;FUMARULO, Ruggiero;
2008

Abstract

Streptococcus pneumoniae is the most common cause of community acquired pneumonia with high morbidity and mortality worldwide. A major feature of pneumococcal pneumonia is an abundant neutrophil (PMNs) infiltration. We have found that the wild-type D39 strain and the CPS2E strain, a non encapsulated isogenic mutant of D39 lacking only the gene cps2E, stimulated superoxide anion (O2-), evaluated by cytochrome c reduction, similarly. But a non-encapsulated R6 strain, containing also a deletion starting from cps B to cps G genes, amplified the oxidative burst. The R6 strain activated neutrophil NADPH oxidase to produce reactive oxygen intermediates, as demonstrated by the traslocation of its cytosolic subunits p47phox to the plasma membrane. This activity was completely inhibited by wortamannin and bisidolylmaleimide but not by SB-203580. Taken together these finding strongly suggest that R6 strain activates pathways involving PKC and PI-3 Kinase dependent reactions. In order to know whether modulation of neutrophil functions induced by R6 strain was selective for oxygen metabolism we studied secretion of -glucoronidase, a marker of degranulation. We have found that PMNs incubated with D39 and R6 strains secreted similar levels of -glucoronidase and their effects were lower than that of the standard agonist fMLP. On the basis of these observations, we conclude that pneumococcal expression of genes cps B, C e D modulates neutrophil respiratory burst activity and thus may facilitate chronic persistent infection by Streptococcus pneumoniae.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/136612
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